Derangement of apoptosis-related lymphocyte homeostasis in systemic sclerosis

Objectives. Both increased and decreased apoptosis may be involved in gener ating autoimmunity. This study addressed the question of whether apoptosis and apoptosis-regulating proteins are altered in systemic sclerosis (SSc). Patients and methods. Peripheral lymphocytes of 39 SSc patients and 47 heal thy control persons were studied for apoptosis, Bcl-2 and Bax levels, expre ssion of Fas (CD95) and activation markers (CD25, HLA-DR) as determined by fluorocytometry. Serum Fas and Fas ligand were measured by ELISA. Results. SSc lymphocytes (mainly CD4(+)) expressed increased amounts of Bcl -2, while Bar was not elevated. Apoptosis rates of SSc lymphocytes were inc reased in unsupplemented medium, but returned to normal in the presence of autologous plasma. SSc patients had increased percentages of activated and CD95(+) lymphocytes and elevated soluble Fas and soluble FasL levels in ser um. Activating anti-CD95 antibodies further increased the apoptosis rate. Conclusions. Increased in vitro apoptosis, elevated lymphocytic Bcl-2 conte nt and the increased number of Fas-positive T cells are not specific for pe ripheral blood from SSc patients, but indicate deregulation of lymphocyte h omeostasis in this disease.